MFR of Paracetamol Oral Suspension IP (125 mg)
TABLE OF CONTENTS
| SNO. | TITLE | Page No |
| 1.0 | PRODUCT DETAILS | |
| 2.0 | MANUFACTURING FORMULA | |
| 3.0 | LIST OF EQUIPMENT | |
| 4.0 | GENERAL PRECAUTIONS | |
| 5.0 | MANUFACTURING INSTRUCTIONS | |
| 6.0 | MANUFACTURING PROCEDURE | |
| 7.0 | FILLING AND PRIMARY PACKING DETAILS | |
| 8.0 | SECONDARY AND TERTIARY PACKING PROCEDURE | |
| 9.0 | FINISHED PRODUCT SAMPLING & ANALYSIS | |
| 10.0 | SHIPPER STRIPING | |
| 11.0 | PROCEDURAL CHANGES | |
| 12.0 | BRAND DETAILS |
1.0 PRODUCT DETAILS:
| Product Name | Paracetamol Oral Suspension IP (125 mg) |
| Product Description | Pink colored, viscous flavored suspension |
| Strength | 125 mg / 5 ml |
| Label claim
|
Each 5 ml contains: Paracetamol IP – 125 mg |
| Batch Size | 3000 Bottles (180 liters) |
| Average Fill | 60 ml |
| Shelf Life | 24 months |
| Storage | Store in a cool, dry and dark place below 250 C |
| Drug Category | NSAIDS (Pain-killers or Analgesics) |
2.0 MANUFACTURING FORMULA:
| Material Name | Grade | Category | Batch Qty.
(In kg) |
| Paracetamol (micronized) | IP | API | 4.500 kg |
| Glycerin | IP | Diluent / Solubilizer | 14.400 kg |
| Sodium Benzoate | IP | Preservative | 0.540 kg |
| Bronopol | IP | Preservative | 0.090 kg |
| CMC Sodium (DVP) | IP | Thickening Agent | 0.180 kg |
| Xanthan Gum (Suspension Grade) | USP | Thickener and Stabilizer | 0.450 kg |
| Sorbitol Solution (70%) | IP | Diluent and Sweetener | 27.000 kg |
| Citric Acid Monohydrate | IP | Antioxidant and PH Modifier | 0.180 kg |
| Aerosil | IP | Thickener and Glidant | 0.360 kg |
| Aspartame | IP | Sweetener | 0.450 kg |
| Saccharin Sodium | IP | Sweetener | 0.180 kg |
| Neotame | IP | Sweetener | 0.009 kg |
| Erythrosine Supra Color | – | Color | 0.009 kg |
| Raspberry Liquid | – | Flavor | 0.540 liter |
| Black Current Liquid | – | Flavor | 0.270 liter |
3.0 LIST OF EQUIPMENTS:
| Sr. No. | Machinery/Equipment | Capacity | Eq. ID |
| 1. | S.S. Mixing Tank with Stirrer | ||
| 2. | Portable Stirrer | 1800 RPM |
|
| 3. | Colloidal Mill | – |
|
| 4. | S.S. Storage Tank | ||
| 5. | S.S. Storage Tank | 200 Liter |
|
| 6. | S.S. Filling Storage Tank | 100 Liter |
|
| 7. | S.S. Storage Tank | 100 Liter | |
| 8. | SS Storage tank (capacity: 500) | 500 Liter | |
| 9. | Filter Cloth | 60 No | |
| 10. | pH Meter | – | |
| 11. | S.S. Spatula | – | |
| 12. | Two Head Semi-Automatic Filling with Sealing machine | 3000 Bottles /hours | |
| 13. | Gum Labeling Machine | 3000 Bottles /hours | |
| 14. | Label Printing Machine | 2500 Labels | |
| 15. | Shipper Striping Machine | – | – |
4.0 GENERAL PRECAUTIONS:
- Paracetamol API Description: White crystals or a white crystalline powder.
- All the Manufacturing Activity shall be performed under control conditions (temperature NMT 25 0C and relative humidity NMT 60%).
- When working with Active Ingredients/ Drug Product/Mixture of Active Ingredients/Excipients wear gloves, mask to avoid exposure and contact to any body parts.
5.0 MANUFACTURING INSTRUCTIONS:
- All activities shall be performed as per current SOPs
- Take the line clearance from QA before starting the manufacturing and packing operation during batch to batch and product to product change over.
- Do not overwrite the entry, in case of mistake, cancel the entry by single line with sign & date and make correct entry.
6.0 MANUFACTURING PROCEDURE:
STEP – I (SOAKING)
Transfer the Glycerin (14.400 kg) in S.S. Storage Tank (capacity: 100 liters) and add (4.500 kg) of
Paracetamol in it by continuously stirring until uniform mixing achieved and hold overnight to let it swell at (temperature NMT 25 0C). After soaking overnight, make a smooth paste/ slurry by stirring with portable stirrer
Total time for Soaking: Overnight (10 to 12 hrs.).
STEP – II:
Separately dissolve Sodium Benzoate IP (0.540 kg), Bronopol IP (0.090 kg) in hot Purified Water (30.00
liter, temperature: 50-60oC) in SS Mixing Tank (capacity: 250 liter) continuously stirring.
STEP-III:
Add CMC Sodium (DVP) IP (0.180 kg), Xanthan Gum (Suspension Grade) USP (0.450 kg) in the mixture of Step – II by continuous stirring. Mix it thoroughly until a smooth paste is formed and hold the mixture for soaking for 01 hours.
Mixing Time: 10 minutes.
Soaking time: 60 minutes.
STEP-IV:
Add (27.00 kg) Sorbitol Solution (70%) in mixture of Step – II continuously stirring.
STEP-V:
Take hot Purified Water (2.0 liter, at 30o-40oC) in SS Container (capacity: 10 liters) & add citric acid (0.180 kg) under stirring with SS Spatula to dissolve and add to mixture of Step – II continuously stirring. Rinse the SS Container with Purified Water (0.2 liter, at 30o-40oC) and add rinsing to the mixture of Step – II.
STEP-VI:
Assemble the colloidal mill and colloid & transfer the slurry of Step-I through colloidal mill in Mixing Tank of step II continuously stirring.
Rinse the Storage Tank with Purified Water (10 liter) and add rinsing to the Mixing Tank of Step II.
Add Aerosil (0.360 kg) in Mixing Tank continuously stirring.
STEP-VII:
Separately dissolve Aspartame (0.450 kg), Saccharin Sodium (0.180 kg) in hot Purified Water (10 liter, temperature: 60o-70oC) in SS Container (capacity: 10 liter) and add to mixture of Step – II in Mixing Tank continuously stirring.
Rinse the SS Container with hot Purified Water (0.5 liter, temperature: 60o-70oC) and add the rinsing in suspension.
STEP-VIII:
Separately dissolve Neotame (0.009 kg) in hot Purified Water (2.0 liter, temperature: 45o– 50oC) in SS Container (capacity: 10 liter) and add to above mixture of Step – II in mixing tank continuously stirring.
Rinse the SS Container with Purified Water (0.5 liter, temperature: 45o– 50oC) and add the rinsing in the suspension.
STEP-IX:
Separately dissolve color Erythrosine Supra (0.009 kg) in hot Purified Water (1.0 liter, temperature: 45oC) in SS Container (capacity: 10 liter) and add to above mixture of Step – II in Mixing Tank continuously stirring.
Rinse the SS Container with Purified Water (0.5 liter, temperature: 45oC) and add the rinsing in the suspension. Cool the suspension to about 40oC.
STEP-X:
Add Raspberry Liquid Flavor (0.540 liter) and Black Current Liquid Flavor (0.270 liter) to the above Mixing Tank in Step – II continuously stirring.
STEP – XI:
Make up the volume of suspension with Purified Water (180 liter, at room temperature) and mix for 10 minutes to get lumps free suspension.
STEP – XII
Filter the suspension through 60# Filter Cloth and transfer the suspension in Storage Tank (capacity: 200 liter).
Volume made to 180 liters.
Mixing Time: 10 minutes.
STEP-XIII:
After completion of filtration, collect the bulk sample from the Storage Tank and send to QC for analysis according to the table below:
| Test | Specification |
| Appearance of bulk
Bulk Assay Weight/ml Density pH limit |
Pink Solution
98 to 102 % 1.15 gm./ml To be established 5.0 to 5.8 |
NOTE:
After completing manufacturing process, clean all equipments and ancillary items as per respective cleaning SOP to prepare for the next batch.
7.0 FILLING AND PRIMARY PACKING DETAILS:
After receiving QC approval for bulk suspension, manually transfer bulk solution from SS Storage tank (capacity: 200 liters) to SS Storage tank (capacity: 500 liters) and start bottle filling and sealing as per the following parameters and in-process checks.
7.1 INITIAL SETTING AND IN-PROCESS PARAMETERS:
| Sr.No. | Parameters | Standard | No. of Bottles | In-Process Frequency |
| 1. | Description | Pink color, viscous flavored suspension. | 06 | 01 hours |
| 2. | Filling Head | Two Head | – | – |
| 3. | Capping & Sealing Head | One Head | – | – |
| 4. | Filling machine speed | 2000 Bottle /Hours | – | – |
| 5. | Sealing machine speed | 2000 Bottle /Hours | – | – |
| 6. | Average Fill Volume | NLT 60 ml | 02 bottles | 30 minutes |
| 7. | Uniformity of Fill Volume | NLT 60 ml | 20 bottles | 30 minutes |
| 8. | Cap locking | Cap should be locked properly | 02 bottles | 30 minutes |
| 9. | Cap sealing | Cap should be sealed properly | 02 bottles | 30 minutes |
| 10. | Pressure Differential | NLT 4 kg | – | – |
| 11. | Leak Test | Leak test should be done properly | 04 bottles | 01 hours |
| 12. | Bottle Size | 60 ml | – | – |
| 13. | Gum labeling machine | 2000 Bottle /Hours | – | – |
DETAILS OF PRIMARY PACKING MATERIAL:
| Sr. No. | NAME OF MATERIALS | QUANTITY |
| 1 | 60 ml. Amber Pet Bottles | 3000 |
| 2 | P.P. Caps (25 mm) | 3100 |
7.3 FILLING AND PRIMARY PACKING PROCEDURE:
STEP-I (BOTTLE DE- CARTONING):
De-carton the pet bottles from corrugated boxes and arrange it in turntable. Start the turntable and conveyor. Bottles will move and pass through an empty visual inspection unit.
STEP-II (EMPTY BOTTLES INSPECTION):
Inspect empty bottles for any damages & cleanliness before filling.
STEP-III (LIQUID FILLING AND SEALING):
Record the temperature of Liquid Filling & Sealing Area. (temperature NMT 25 0C and relative humidity NMT 60%).
Transfer the bulk suspension from SS Storage tank (capacity: 500 liters) to Liquid Filling Tank (capacity: 100 liter) by pipe line through gravity.
Adjust the volume of the suspension with the help of screw on the filling cylinder.
Set volume at 60 ml. and check the filled volume through the measuring cylinder. If filling volume is within limit (NLT 60 ml + 2 ml).Start the filling operation.
If filling volume is out of limit, again adjust the volume.
Reject the first two to four bottle stroke of liquid while setting of volume.
Load the PP Cap to the hopper of sealing machine and PP Caps moves to bottle head through shoot of machine.
Adjust the Sealing Machine as per size of PP cap (25 mm).
After Filling and Sealing Machine setting, start the Liquid Bottle Filling and Sealing Operation.
Monitor the in-process parameters mentioned in Step- 7.1 during Filling and Sealing Operation & record.
8.0 SECONDARY AND TERTIARY PACKING PROCEDURE:
8.1DETAILS OF SECONDARY AND TERTIARY PACKING MATERIAL:
| Sr. No. | NAME OF MATERIALS | QUANTITY |
| 1 | Label | 3100 |
| 2 | Measuring Cups (10 ml) | 3000 |
| 3 | Corrugated Box (60 x100) | 30 |
| 4 | Jalli | 60 |
| 5 | Top | 30 |
STEP-I (VISUAL INSPECTION):
Perform visual inspection of filled & sealed bottles for damages, improper sealing, low / high volume and foreign particles.
Transfer the good inspected bottles through conveyor for labeling & packing.
Keep aside all the bottles from rejection like improper sealing & low/high volume & recover the liquid by filter through 60# filter cloth & add it to Filling Tank.
Rejection like damaged bottles and bottles with foreign particles are to be destroyed in presence of QA.
After completion of the operation (filling and sealing) fill 100 liter Purified Water (Room temperature) in Storage Tank and circulate water for 10 minutes and then drain out completely.
Clean all Machines properly as per respective cleaning SOPs.
STEP-II (MEASURING CUP PLACING):
Put Measuring cup manually on the bottles and press the measuring cups by hands, so that measuring cups are fit properly on the bottles.
STEP-III (LABELS CODING PROCEDURE):
Clean the Domino Printing Machine as per respective SOP.
Take the Line Clearance from IPQA.
Transfer the labels to Printing room from Store.
Re ensures the number of labels received for overprinting with status label.
Set the Batch details (Batch No., Mfg Date., Exp Date and MRP.) in Domino Printing machine and verify the details in PLC display.
Take the specimen sample of printed labels and checked by Production Supervisor for correctness of Batch details and match with Batch Planning sheet and will be counter checked by IPQA.
After approval affix, specimen sample of printed labels to batch record and start labels coding.
After labels coding, keep the printed labels in bundles and store in racks, affix the status label “Ready For Packing” with Batch Details and transfer Secondary Packing of Liquid Section.
Keep the rejected quantity of labels separately for destruction with proper status label “Rejected”.
STEP-III (BOTTLE LABELING AND PACKING):
Clean the Labeling Machine as per respective SOP.
Take the Line Clearance from IPQA.
Set the labeling machine for the required label size (60 ml).
Start labeling machine and start the pasting of batch coded labels on bottles.
Check each labeled bottle for proper labeling & printing.
Pack the 100 labeled bottles in one corrugated box.
Finally close the corrugated box with BOPP tape and affix box label on corrugated box & weigh it.
After the completion of packing operation, calculate the batch yield (Limit: NLT 97% to NMT 100%)
Reconcile the packing material. Return the excess packing material to Packing Material Store with PPC
Destroy all rejected printed packing materials in the presence of IPQA.
Transfer the finished product to Finished Goods Store.
9.0 FINISHED PRODUCT SAMPLING & ANALYSIS:
After completion of packing, collect the Finished Product sample (01 bottle) and control sample (05 bottles) from packing line and send to QC for analysis as per approved finished specification.
10.0 SHIPPER STRIPING:
In Finished Goods Store strip all packed shipper with the help of Shipper Stripping Machine and inform to sales department for billing and dispatch.
11.0 PROCEDURAL CHANGES:
If the production department has compelling reasons for modifying this manufacturing procedure, it should proceed only after approval from Quality Assurance Department.
NOTE
After completion of the packing operation, clean equipment and packing area as per respective cleaning SOPs, to prepare for the next batch.
MFR of Paracetamol Oral Suspension IP (125 mg)